Published in:
Open Access
01-11-2015 | Original Paper
Reducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies
Authors:
Jens Wagner, Sybille Krauss, Song Shi, Sergey Ryazanov, Julia Steffen, Carolin Miklitz, Andrei Leonov, Alexander Kleinknecht, Bettina Göricke, Jochen H. Weishaupt, Daniel Weckbecker, Anne M. Reiner, Wolfgang Zinth, Johannes Levin, Dan Ehninger, Stefan Remy, Hans A. Kretzschmar, Christian Griesinger, Armin Giese, Martin Fuhrmann
Published in:
Acta Neuropathologica
|
Issue 5/2015
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Abstract
Pathological tau aggregation leads to filamentous tau inclusions and characterizes neurodegenerative tauopathies such as Alzheimer’s disease and frontotemporal dementia and parkinsonism linked to chromosome 17. Tau aggregation coincides with clinical symptoms and is thought to mediate neurodegeneration. Transgenic mice overexpressing mutant human P301S tau exhibit many neuropathological features of human tauopathies including behavioral deficits and increased mortality. Here, we show that the di-phenyl-pyrazole anle138b binds to aggregated tau and inhibits tau aggregation in vitro and in vivo. Furthermore, anle138b treatment effectively ameliorates disease symptoms, increases survival time and improves cognition of tau transgenic PS19 mice. In addition, we found decreased synapse and neuron loss accompanied by a decreased gliosis in the hippocampus. Our results suggest that reducing tau aggregates with anle138b may represent an effective and promising approach for the treatment of human tauopathies.